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• W1991058282 abstract "HIV post-exposure prophylaxis (PEP) with antiretroviral drugs after occupational exposure to HIV has become well established after it was shown that monoprophylaxis with zidovudine may reduce the risk of HIV transmission by approximately 80% [1]. However, PEP after non-occupational exposure is still controversial. Among the problems encountered after non-occupational exposures are: establishing the HIV serostatus of the source; uncertainties about the seriousness of exposure; a longer time lag until the onset of prophylaxis than with occupational exposures; and the potential of repeated or unreported exposures. Also it is unclear whether PEP after mucosal HIV exposure is as efficient as after parenteral exposure. Here we report an acute HIV infection of the previously seronegative partner of a serodiscordant couple, which was diagnosed 2 weeks after the completion of a 4-week course of PEP initiated after sexual exposure. Case report Patient A (source) was diagnosed with an acute retroviral syndrome in 1999. Highly active antiretroviral therapy (HAART) was started shortly after HIV diagnosis, with zidovudine, lamivudine and nelfinavir. HAART was continued for 12 months and nelfinavir was replaced by efavirenz after 4 months. The viral load decreased below 50 copies/ml. In April 2000, treatment was discontinued upon patient request. Viral load rebounded to 30 000 copies/ml and fluctuated in the following months between 6000 and 25 000 copies/ml, the CD4 cell count was stable at approximately 600 cells/μl (19%). Patient B tested negative for HIV antibodies in 1999. In July 2001, he started a relationship with patient A. Both patients had sexual contacts with additional partners. In December 2001, patient B reported an episode of unprotected insertive anal intercourse of short duration without ejaculation with patient A. In November 2001, the viral load of patient A had been 20 000 copies/ml. Four hours after the intercourse both partners presented for HIV risk counselling in a specialized HIV practice. After counselling, patient B immediately started PEP with a combination of stavudine, didanosine and lopinavir/ritonavir. The baseline HIV antibody test was negative. The PEP regimen was regularly taken during 4 weeks. Two weeks after the cessation of PEP patient B presented with a rash (trunk and extremities) and fever up to 39°C. The first symptoms were observed one week before presentation. HIV polymerase chain reaction revealed a viral load greater than 750 000 copies/ml, the CD4 cell count was 400 cells/μl (5.5%), HIV serology was not analysed. Two weeks later (13 February 2002), a blood sample was HIV antibody positive in two HIV enzyme-linked immunosorbent assay tests, and the Western blot revealed antibodies to gp160, p55 and p24. This blood sample as well as a sample from patient A (8 March 2002) were analysed for genotypic resistance. Because of a developing neuritis of nervus facialis, recurrent fever attacks up to 39°C and myalgia, patient B started HAART with lamivudine, abacavir and efavirenz (ZODIAC trial) a few days later. The symptoms improved within 2 weeks, treatment was well tolerated, the CD4 cell count increased to 550 cells/μl (30%), and the viral load decreased from 8 000 000 copies/ml to undetectable levels after 12 weeks of therapy. Both viruses were drug-sensitive as predicted from the genotypic resistance analysis (pol sequence) [2]. Only a few identical resistance-associated mutations in the protease and none in the reverse transcriptase genes were identified (protease L10I, M36I, A71I). The HIV subtype was classified by phylogenetic analysis using the neighbour joining method [3]. Both HIV isolates belonged to subtype B (Fig. 1) and were very closely related (bootstrap value 100%; Fig. 1). The nucleotide divergence between the two isolates was much lower (0.4 %) compared with subtype B reference strains (intrastrain divergence 2.6–4.5%) or ur unrelated subtype B infections (2.8–7.0%). The data clearly indicate a linked infection event.Fig. 1. Subtyping of the: pol sequence by phylogenetic analysis (neighbour joining tree). Pol sequences of the reference viruses for HIV-1 groups M, N, O and M – subtypes of the HIV Los Alamos database (reference alignment of pol 2001, http://hiv-web.lanl.gov/content/hiv.db/SUBTYPE_REF/align.html) and the pol sequences of patients A and B were aligned with CLUSTALW (version 1.7, [7]). After endtrimming of the alignment (final length corresponds from position 2253 to 3438 in reference sequence pNL4.3 acc. no. M19921; 99 aa protease and 296 aa reverse transcriptase) a neighbour joining tree was constructed based on the distance matrix (DNAdist, Kimura 2 parameter model) of the alignment and using CPZgab (acc. no. X52154) as the outgroup (PHYLIP package version 3.5c Felsenstein 1993 [3]). The monophyletic clades of the HIV-1 subtypes and the circulating recombinant forms were indicated by brackets. The pol sequences of patients A (02–0036) and B (02–0052) are boxed by dashed lines (arrow). The bar length represents 10% nucleotide exchanges per position of the alignment. Bootstrap analysis was performed using 1000 replicates. The numbers at the nodes of the tree represent the percentage of analyses in which the sequences branch off the same node (common ancestor). Values greater than 70% are considered to be significant.We can only speculate about the reason for PEP failure. If the reported event was indeed the transmission event, failure may have been related to the mode of transmission. The first cells to come into contact with HIV during insertive anal intercourse would be Langerhans cells in the foreskin and penile mucosa. HIV can be internalized into these cells, retaining its infectivity for an extended period of time and remaining protected from the effects of antiretroviral drugs [4–6]. After the cessation of PEP, surviving sequestered virus from these cells could ignite viral replication cycles and establish systemic infection. On the other hand, it cannot be excluded that transmission occurred unnoticed at an earlier timepoint before the start or, alternatively, by oral intercourse during or immediately after the termination of the PEP regimen. If transmission occurred before the reported exposure, patient B would have been in the serological window period at first presentation." @default.
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• W1991058282 date "2004-02-01" @default.
• W1991058282 modified "2023-09-25" @default.
• W1991058282 title "HIV transmission despite HIV post-exposure prophylaxis after non-occupational exposure" @default.
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• W1991058282 doi "https://doi.org/10.1097/00002030-200402200-00036" @default.
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